Monoclonal antibodies (mAbs), which are emerging as promising disease-modifying treatments for Alzheimer’s disease (AD), come with significant challenges associated with their accessibility. The technology to identify the pathological features of AD and safe administration of mAb therapies currently limit their access globally, with Japan being no exception. While the positive top-line results from Clarity AD, the global Phase III clinical trial for Eisai and Biogen’s lecanemab, provide hope for its regulatory success, accessibility issues are likely to limit its uptake post-approval in Japan, says GlobalData, a leading data and analytics company.

According to GlobalData’s ‘Pharmaceutical Intelligence Center’, the total number of diagnosed prevalent cases of AD in Japan is expected to increase from 2.5 million in 2021 to 3.0 million in 2028, representing a compound annual growth rate of 2.64%.

Based on the primary research previously conducted by GlobalData, the diagnosis rate for early AD is very low (16.9% for mild cognitive impairment [MCI] and 31.1% for mild AD) among patients aged ≥60 years in Japan. Along with the difficulty of identifying and diagnosing these earlier forms of the disease, low diagnosis rates may also be a product of a limited number of facilities able to conduct amyloid positive emission tomography (PET) or spinal fluid tests by lumbar puncture in addition to ordinary cognitive function tests needed to initiate treatment.

Neha Myneni, Pharma Analyst at GlobalData, comments: “Despite the increasing prevalence of AD in Japan and the need for disease-modifying treatments like the anti-amyloid beta (Aβ) mAbs, there are likely to be various healthcare challenges that will limit the uptake of these drugs. These include shortages of authorized facilities to conduct diagnostic tests and limited access to such facilities, lack of skilled personnel and infusion centres to initiate the treatment, and cost (attributed to frequency of infusion and regular follow-up magnetic resonance imaging [MRIs] for adverse event monitoring), among others.”

The most significant adverse event associated with lecanemab and other late-stage anti-Aβ mAbs being developed for AD (Eisai and Biogen’s aducanumab-avwa, Eli Lilly’s donanemab and solanezumab, and Roche’s gantenerumab) is amyloid related imaging abnormalities (ARIA), seen commonly as temporary swelling/effusion of the brain (ARIA-E) and in some cases small spots of bleeding in or on the surface of the brain (ARIA-H) along with the swelling. Though lecanemab’s overall ARIA incidence profile was within the expectations in the Clarity AD clinical trial, patients taking the drug will need continued monitoring through follow up MRIs, and hence is likely to only be used by specialists.

Myneni concludes: “The treatment for AD is more commonly offered by geriatricians, geriatric psychiatrists, general practitioners, and internal medicine specialists. However, as mAb therapies are most likely to be initiated and monitored by neurologists, the lack of educated and trained personnel specialized in AD diagnosis and care in Japan is expected to affect their uptake. Hence, a collaborative effort between various neurology organisations and national associations in the country could help address the accessibility challenges associated with mAb therapies and make them available for eligible AD patients.”